The overall long term goals of the proposed research are three-fold: 1) to continue studies on the mechanisms and the dynamics of the secretion of pancreatic islet cell hormones and growth hormone in response to nutrients and pharmacological agents and studies on the nature of their secreted and stored forms in health and disease; 2) to obtain further information on the mechanism and dynamics of islet cell hormone secretion by utilization of the perfused pancreas of nondiabetic and diabetic animals; and 3) to complement studies of hormone secretion by studies on cell-hormone receptors in health and disease. These objectives will be fulfilled by studies carried out in vivo in man and dogs, as well as in the isolated perfused rat pancreas. In addition lymphocyte receptor assays will be developed for the study of the interaction of peptide hormones with their cell receptors in health and disease.